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Objective To investigate the effects of hypoxia inducible factor-1α (HIF-1α) on the brain injury of necrotizing enterocolitis (NEC) mice. Methods Eighty-one C57BL/6 mice aged 5 d were randomly divided into 4 groups: Control group (CON, n=15, breastfed, in cages with their mothers), NEC group (n=24, fed in an incubator, with formula milk+hypoxia+oral lipopolysaccharide to induce NEC mouse model), DMOG group (n=19, given HIF-1α stabilizer DMOG on the base of NEC model), and 2ME2 group (n=23, given HIF-1α inhibitor 2ME2 on the base of NEC model). The mortality of mice was recorded during modeling. All mice were sacrificed in 4 d after modeling, and the intestinal pathological features of mice were observed by HE staining. Western blotting and immunohistochemical assay were performed respectively to detect the expression of HIF-1α protein in brain tissue and the numbers of activated microglia, astrocytes and oligodendrocytes in the hippocampus. The mRNA levels of inflammatory cytokines IL-1β and TNF-α were determined by RT-qPCR in brain tissue. Results As compared with the CON group, the mice of the NEC group showed intestinal tract damage, increased activated microglia (0.80±0.75 vs 4.00±0.63, P < 0.05) and astrocytes (P < 0.05) in the hippocampus, decreased number of oligodendrocytes (64.40±7.26 vs 45.60±2.80, P < 0.05), and higher levels of TNF-α, IL-1β and HIF-1α (P < 0.05). After intraperitoneal injection of HIF-1α stabilizer DMOG, the survival rate of mice in the DMOG group was increased (66.67% vs 84.21%, P < 0.05), and the intestinal injury was reduced. The activation of microglia (4.00±0.63 vs 1.60±0.49, P < 0.05) and astrocytes (P < 0.05) was inhibited, while the number of oligodendrocytes was elevated (45.60±2.80 vs 56.00±5.22, P < 0.05), and the expression of TNF-α and IL-1β was down-regulated (P < 0.05). However, intraperitoneal injection of HIF-1α inhibitor 2ME2 resulted in opposite outcomes. Conclusion HIF-1α is protectively up-regulated in the brain of NEC mice, and its stable and high expression reduces the neuroinflammation in the brain of NEC mice, exerting a protective effect on the brain.

The high-fat diet would lead to excessive fat storage in the liver to form metabolic dysfunction-associated steatotic liver disease (MASLD), and the trend is burgeoning. The aim of the study is to investigate the effects of chlorogenic acid (CGA) on metabolites and gut microorganisms in MASLD mice induced by a high-fat diet. In comparison to the HF group, the TC (total cholesterol), TG (total triglycerides), LDL-C (low-density lipoprotein cholesterol), AST (aspartate aminotransferase) and ALT (alanine transaminase) levels were reduced after CGA supplement. CGA led to an increase in l-phenylalanine, l-tryptophan levels, and promoted fatty acid degradation. CGA increased the abundance of the Muribaculaceae, Bacteroides and Parabacteroides. Changes in these microbes were significantly associated with the liver metabolites level and lipid profile level. These data suggest important roles for CGA regulating the gut microbiota, liver and caecum content metabolites, and TG-, TC- and LDL-C lowering function. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) has been linked to congenital heart disease and fetal alcohol syndrome. The heart primarily relies on mitochondria to generate energy, so impaired mitochondrial function due to alcohol exposure can significantly affect cardiac development and function. Our study aimed to investigate the impact of PAE on myocardial and mitochondrial functions in offspring mice. Methods: We administered 30% alcohol (3 g/kg) to pregnant C57BL/6 mice during the second trimester. We assessed cardiac function by transthoracic echocardiography, observed myocardial structure and fibrosis through staining tests and electron transmission microscopy, and detected cardiomyocyte apoptosis with dUTP nick end labeling assay and real‐time quantitative PCR. Additionally, we measured the reactive oxygen species content, ATP level, and mitochondrial DNA copy number in myocardial mitochondria. Mitochondrial damage was evaluated by assessing the level of mitochondrial membrane potential and the opening degree of mitochondrial permeability transition pores. Results: Our findings revealed that PAE caused cardiac systolic dysfunction, ventricular enlargement, thinned ventricular wall, cardiac fibrosis in the myocardium, scattered loss of cardiomyocytes, and disordered arrangement of myocardial myotomes in the offspring. Furthermore, we observed a significant increase in mitochondrial reactive oxygen species content, a decrease in mitochondrial membrane potential, ATP level, and mitochondrial DNA copy number, and sustained opening of mitochondrial permeability transition pores in the heart tissues of the offspring. Conclusions: These results indicated that PAE had adverse effects on the cardiac structure and function of the newborn mice and could trigger oxidative stress in their myocardia and contribute to mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

There is significant interest in using postbiotics as an intervention strategy to address obesity. This study assesses the efficacy of postbiotics derived from different sourdough strains ( Lactiplantibacillus plantarum LP1, LP25, and Pediococcus pentosaceus PP18) in mitigating intestinal injury in zebrafish fed on a high-fat diet. We screened postbiotics for their anti-colon cancer cell effects and compared various preparation methods applied to live bacterial strains, including heat-killing at different temperatures, pH adjustments, and ultraviolet radiation exposure. Heat-killing at 120 °C proved to be the most effective preparation method. A marked variation in health effects was observed in the heat-killed microbial cells, as evidenced by their hydrophobicity and self-aggregation ability. A five-week high-fat dietary intervention study in zebrafish demonstrated that diets supplemented with 10 8 CFU g -1 K-LP25 significantly attenuated weight gain and body fat, along with reductions in FASN , Leptin , and SREBF1 mRNA expression. However, diets supplemented with 10 7 CFU g -1 K-PP18 only reduced Leptin and SREBF1 mRNA expression. K-PP18 was more effective at mitigating gut barrier damage, promoting colonic Occludin , ZO-1 , and Claudin-1 levels. Additionally, K-LP25 supplementation markedly downregulated the pro-inflammatory cytokines TNF-α , IL-6 , and IL-1β , reducing intestinal inflammation. Supplementation with K-LP1 and K-PP18 increased the abundance of Acinetobacter spp., whereas K-LP25 increased the abundance of Cetobacterium and Plesiomonas . Collectively, these findings suggest that inactivated strains confer protective effects against high-fat diet-induced intestinal damage in zebrafish, with variation observed across different species. Studying the effects of sourdough-derived postbiotics on gut health may open new avenues for dietary interventions to manage gut-related diseases.